Five million Americans suffer from heart failure and 250,000 die from the disease each year. Left ventricular (LV) remodeling caused by a myocardial infarction (MI) is now responsible for almost 70% of the 5 million cases of heart failure in the United States. Gheorghiade M, Bonow R O. Chronic heart failure in the United States: a manifestation of coronary artery disease. Circulation 1998; 97:282-289. In most cases patients who survive a myocardial infarction are initially asymptomatic, however, many develop progressive heart enlargement, loss of heart function and symptoms of heart failure over the ensuing months and years after their initial heart attack. This progressive process is termed ventricular remodeling. In spite of modern medical and surgical treatment the 5 and 8 year mortality after symptoms of heart failure develop is 50% and 80%, respectively.
Immediately after a heart attack the affected region of heart muscle stops contracting and stretches as the remainder of the heart continues to contract. This stretching is termed infarct expansion. Early infarct expansion, or stretching, has been associated with adverse remodeling and a poor long-term prognosis. Erlebacher J A et al., Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement. J Am Coll Cardiol 1984; 4:201-208; Eaton L W et al., Regional cardiac dilatation after acute myocardial infarction. N Engl J Med 1979; 300:57-62; Weisman H F, Healy B. Myocardial infarct expansion, infarct extension, and reinfarction: pathophysiologic concepts. Prog Cardiovasc Dis 1987; 30:73-110. In previous experimental studies using sonomicrometry (Jackson B M et al., Extension of borderzone myocardium in postinfarction dilated cardiomyopathy. J Am Coll Cardiol 2002; 40:1160-1167), echocardiography (Lima J A et al., Impaired thickening of nonischemic myocardium during acute regional ischemia in the dog. Circulation 1985; 71:1048-1059; Jackson B M, et al. Border zone geometry increases wall stress after myocardial infarction: contrast echocardiographic assessment. Am J Physiol 2003; 284: H475-H479), and magnetic resonance imaging (Kramer C M et al., Regional differences in function within noninfarcted myocardium during left ventricular remodeling. Circulation 1993; 88:1279-1288; Epstein F H et al., MR tagging early after myocardial infarction in mice demonstrates contractile dysfunction in adjacent and remote regions. Magn Reson Med 2002; 48: 399-403; Pilla J J et al., Early post infarction ventricular restraint improves borderzone wall thickening dynamics during remodeling. Ann Thorac Surg 2005; 80:2257-2262), infarct expansion has been shown to result in stretching and decreased contractile function in the neighboring normally perfused borderzone (BZ) myocardium. Additionally, while the perfused but hypocontractile myocardium is initially isolated to the region immediately adjacent to the infarct, the process extends with time to involve progressively more myocardium remote from the infarcted region. Jackson B M et al. (2002); Ratcliffe M B. Non ischemic infarct expansion. J Am Coll Cardiol 2002; 40: 1168-1171.
Thus, infarct expansion initiates and sustains the progression to symptomatic heart failure. A safe and effective therapy that could be deployed early after a heart attack which could prevent progressive heart dilatation and loss of function would be of great value.
Currently patients who suffer a heart attack are treated with medications such as beta adrenergic blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers. These classes of drugs have modest beneficial effects on survival that tend to deteriorate over time. Improved drug and device based treatments are, therefore, being sought aggressively. Cell therapy treatments could yield positive results; however, while significant advances have been made in cardiac cell therapy, definitive therapeutic benefits have been difficult to demonstrate conclusively despite numerous clinical trials.
Certain mechanical means for restraining the size of the heart have been developed. Acorn Cardiovascular, Inc. (St. Paul, Minn.) has developed a mesh restraint device for wrapping the heart in patients with established heart failure. This product requires major surgery for placement and has failed to gain FDA approval. It has never been placed clinically in the early postinfarction period. Paracor Medical Inc. (Sunnyvale, Calif.) has developed a nitinol mesh for restraining the heart. Like the device developed by Acorn Cardiovascular, this product requires surgical placement and is intended for patients with established heart failure. The Paracor device is in phase II clinical trials.
Methods that involve the injection of blood plasma and cellular derivatives in order to provide (or induce) structural reinforcement for injured cardiac tissue are disclosed by Nayak et al. in U.S. Pub. No. 2007/0093748. Nayak et al. used platelet rich plasma, alone or in a gelled combination with clotting agents, to ameliorate cardiac remodeling.
There remains an unmet need for systems and methods for the regulation of post-infarct cardiac expansion other than cell therapy regimens, mesh restraint devices, and injection of blood plasma and cellular derivatives.